TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti

The auditory function of the mammalian cochlea relies on two types of mechanosensory hair cells and various non-sensory supporting cells. Recent studies identified the transcription factors INSM1 and IKZF2 as regulators of outer hair cell (OHC) fate. However, the transcriptional regulation of the differentiation of inner hair cells (IHCs) and their associated inner supporting cells (ISCs) has remained enigmatic. Here, we show that the expression of the transcription factor TBX2 is restricted to IHCs and ISCs from the onset of differentiation until adulthood and examine its function using conditional deletion and misexpression approaches in the mouse. We demonstrate that TBX2 acts in prosensory progenitors as a patterning factor by specifying the inner compartment of the sensory epithelium that subsequently gives rise to IHCs and ISCs. Hair cell-specific inactivation or misexpression causes transdifferentiation of hair cells indicating a cell-autonomous function of TBX2 in inducing and maintaining IHC fate.

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Andreas Kispert, Mark-Oliver Trowe Nov 16, 2022 Images of of sections were acquired using a Leica DM5000 microscope with a Leica DFC300FX digital camera and Leica Firecam for Mac 1.9 software, or or a Leica DM6000 microscope with a Leica DFC350FX digital camera and Leica Application Suite X (3.0.1) software. Images of of cochlea whole-mount specimen were acquired using the confocal laser scanning microscope Leica TCS SP8 with Leica Application Suite X 3.5.5 software. Microarray data were obtained using the Agilent Micro Array Scanner G2565CA system. Data Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: -Accession codes, unique identifiers, or web links for publicly available datasets -A description of any restrictions on data availability -For clinical datasets or third party data, please ensure that the statement adheres to our policy Field-specific reporting Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

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All studies must disclose on these points even when the disclosure is negative. No statistical methods were used to predetermine sample size. We used a minimum of 3 animals for each analyses based on the availability of our KO and ME animals. For statistical analyses, we calculated all analyses based on n = the number of cochleae used. For E14.5 microarray experiments we used 4 mutant pools and 4 control pools with 23-27 cochlea each. For E18.5 microarray experiments we used 4 mutant pools and 4 control pools with 16-20 organs of Corti each.
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